Coadministration of seasonal influenza vaccine and MVA-NP+M1 simultaneously achieves potent humoral and cell-mediated responses

Abstract

Current seasonal influenza vaccines have reduced immunogenicity and are of suboptimal efficacy in older adults. We have previously shown that the novel candidate vaccine MVA-NP+M1 is able to boost memory T cell responses in adults aged 50-85 years. Preclinical studies have demonstrated that viral vectored vaccines can act as adjuvants when coadministered with protein-based vaccines. We have conducted a phase I clinical trial to compare the coadministration of seasonal influenza vaccine and MVA-NP+M1 with seasonal influenza vaccine alone in adults aged 50 years and above. This combination of vaccines was safe and well tolerated. T cell responses to internal influenza proteins were boosted to significantly higher levels in the group receiving MVA-NP+M1 compared with the group receiving seasonal influenza vaccine alone. Rates of seroprotection and seroconversion against the three vaccine strains were similar in both groups; however, there was a significant increase in the geometric mean titer ratio for the H3N2 component of seasonal influenza vaccine in the coadministration group. While some vaccine combinations result in immune interference, the coadministration of MVA-NP+M1 alongside seasonal influenza vaccine is shown here to increase some influenza strain-specific antibody responses and boost memory T cells capable of recognizing a range of influenza A subtypes.

Figure 1

Vaccine safety and reactogenicity. The proportion of volunteers experiencing local (a) and systemic (b) adverse events. Only adverse events with possible, probable or definite causal relationships are shown.

Figure 2

T cell responses to NP and M1 as determined by IFN-γ ELISpot. Median responses are shown with error bars indicating IQR. Volunteers in group 1 (open circles) demonstrate a greater peak T cell response than the volunteers in group 2 (closed squares). Historical data from 30 volunteers above the age of 50 receiving MVA-NP+M1 alone are also shown for comparison (dashed lines). This historical data had comparable population demographics (mean age = 65.8 years and proportion of females = 57%). IFN-γ ELISpot, interferon-γ enzyme-linked immunosorbent spot; IQR, interquartile range; M1, matrix protein 1; MVA, modified vaccinia virus Ankara; NP, nucleoprotein.

Figure 3

Antibody responses to TIV as measured by anti-TIV ELISA. Lines with error bars indicate group means and 95% confidence intervals. Fold change in ELISA units in volunteers receiving TIV coadministered with MVA-NP+M1 (open circles) and volunteers receiving TIV and placebo (open squares). ELISA, enzyme-linked immunosorbent assay; M1, matrix protein 1; MVA, modified vaccinia virus Ankara; NP, nucleoprotein; TIV, trivalent-inactivated influenza vaccine.